Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers

A Randomised Phase II Study Of nab-paclitaxel In Combination With Carboplatin As First Line Treatment Of Gastrointestinal Neuroendocrine Carcinomas

Query!

Scientific title

A phase II study to establish if carboplatin and nab-paclitaxel combination is an effective and tolerable chemotherapy treatment for grade 3 advanced gastrointestinal Neuroendocrine Carcinomas.

Query!

Secondary ID [1]2891630

AG0215NET

Query!

Universal Trial Number (UTN)

Query!

Trial acronym

NABNEC

Query!

Linked study record

Query!

Health condition

Health condition(s) or problem(s) studied:

Gastrointestinal Neuroendocrine Carcinomas 2986930

Query!

Condition category

Condition code

Cancer29874929874900

Query!

Neuroendocrine tumour (NET)

Query!

Intervention/exposure

Study type

Interventional

Query!

Description of intervention(s) / exposure

Those randomised to the experimental arm will receive:Intravenous nab-paclitaxel 100 mg/m2 on Day 1 every week and intravenous carboplatin (area under curve equals 5) as per the Calvert formula on Day 1 every 3 weeks until disease progression or unmanageable toxicity.

Query!

Intervention code [1]2946890

Treatment: Drugs

Query!

Comparator / control treatment

Those randomised to the control arm will receive:Intravenous etoposide 100mg/m2 on Days 1-3 every 3 weeks and intravenous carboplatin (area under curve equals 5) as per the Calvert formula on Day 1 every 3 weeks until disease progression or unmanageable toxicity.

The time point for objective tumour response rate (RR is 6 months after the last patient has been enrolled)

Query!

Secondary outcome [1]3236130

To determine the rate of progression free survival (PFS)

Query!

Timepoint [1]3236130

Progression free survival (PFS) will be measured from date of patient randomisation to the date of first evidence of disease progression, the occurrence of new disease or death from any cause. In patients who received treatment on study without a progression date or death, the PFS will be censored on the date of last clinical assessment, tumour assessment or enrolment, whichever is the later event. Disease progression is defined according to the RECIST version 1.1 criteria. The time point for PFS is 6 months after the last patient has been enrolled

Query!

Secondary outcome [2]3236140

To determine overall survival (OS)

Query!

Timepoint [2]3236140

Overall survival (OS) is defined as the interval from the date of randomisation to date of death from any cause, or the date of last known follow-up alive. The time point for OS is 3 years after the last patient has stopped treatment.

Query!

Secondary outcome [3]3236150

To determine safety

Query!

Timepoint [3]3236150

The NCI Common Terminology Criteria for Adverse Events version 4.03 (NCI CTCAE v4.03) will be used to classify and grade the intensity of adverse events after each treatment cycle. This outcome may be assessed until 30 days +/- 7 days after the last dose of treatment.

Query!

Secondary outcome [4]3236160

To assess quality of life (QoL) using the EORTC QLQ C30 and QLQ-GINET21 questionnaires.

Query!

Timepoint [4]3236160

Quality of life is assessed every 3 weeks until progression.

Query!

Secondary outcome [5]3244060

To investigate blood biomarkers as prognostic and/or predictive biomarkers for clinical endpoints including but not limited to circulating tumour cells (enumeration and molecular characterisation) (association of blood biomarkers with clinical endpoints). This is an exploratory outcome.

Query!

Timepoint [5]3244060

At the end of the trial (when the clinical endpoints are available)

Query!

Secondary outcome [6]3244070

To investigate tissue biomarkers as prognostic and/or predictive biomarkers for clinical endpoints including but not limited to biomarkers of cell proliferation, adhesion and metastasis, NEC tumour cell molecular characterisation (association of tissue biomarkers with clinical endpoints). This is an exploratory outcome.

Query!

Timepoint [6]3244070

At the end of the trial (when the clinical endpoints are available)

Query!

Secondary outcome [7]3244080

To investigate the mutational profile and DNA methylation profile and utility in prognosis (association of profiles with clinical outcomes). This is an exploratory outcome - method to be confirmed.

Query!

Timepoint [7]3244080

At the end of the trial (when the clinical endpoints are available)

Query!

Secondary outcome [8]3244090

To investigate the utility of FDG-PET imaging as an early predictor of response (association of early imaging characteristics with RR). This is an exploratory outcome.

Query!

Timepoint [8]3244090

At the end of the trial (when the clinical endpoints are available)

Query!

Secondary outcome [9]3244100

To investigate the clinical utility of functional imaging by FDG PET and 68Ga-octreotate PET/CT Scan (association of imaging with PFS and OS). This is an exploratory outcome.

Query!

Timepoint [9]3244100

At the end of the trial (when the clinical endpoints are available)

Query!

Eligibility

Key inclusion criteria

-Adults, aged 18 years and older, with advanced and/or metastatic, unresectable neuroendocrine carcinoma -Histologically proven (WHO/ ENET) Grade 3 NEC with Ki-67 greater than 20%. (The features of small versus large cell NEC carcinoma will need to be documented and participants with Mixed AdenoneuroEndocrine Carcinomas (MANEC) are eligible if they have G3 elements) -Tumour sufficiently FDG-avid on the initial staging PET Scan (SUVmax minimum 3.5) -Measurable disease as assessed by CT scan of the chest, abdomen and pelvis within 21 days prior to commencement of study treatment (according to RECIST 1.1)-ECOG performance status 0-2-Adequate bone marrow function (platelets greater than 100 x 109/L; ANC greater than 2 x 109/L; haemoglobin greater than 100 x 109/L)-Adequate liver function (total bilirubin less than or equal to 1.5 x ULN, ALT/AST less than or equal to 2.5 × ULN, alkaline phosphatases less than or equal to 2.5 ULN). For participants with liver metastases use the following ULN: total bilirubin less than or equal to 2 x ULN, ALT/AST less than or equal to 3.5 × ULN, alkaline phosphatases less than or equal to 3.5 ULN.-Adequate renal function (creatinine less than or equal to 1.5 ULN) -Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments -Signed, written informed consent (main study)

Query!

Minimum age

18Years

Query!

Query!

Maximum age

No limit

Query!

Query!

Gender

Both males and females

Query!

Can healthy volunteers participate?

No

Query!

Key exclusion criteria

-NECs confirmed not to be from gastrointestinal primaries-Grade 1 and Grade 2 NETs (Ki-67 less than or equal to 20%)-Suspected pulmonary origin of the NET -Known hypersensitivity to nab-paclitaxel-External beam radiotherapy to solitary target lesions. Patients who have received local radiotherapy of non-target lesions for local symptom control within the last 4 weeks must have recovered from any adverse effects of radiotherapy prior to randomization.-Prior intrahepatic 90Y-microspheres such as SIR-Spheres-Major surgery/surgical therapy for any cause within 1 month -Surgical therapy of loco-regional metastases within the last 3 months prior to randomization-Severe cardiovascular, hepatic, neurologic or renal comorbid conditions-Previous cytotoxic chemotherapy, or targeted therapy, or biotherapy within the last 4 weeks (excluding SSAs)-Significant infection, including chronic active hepatitis B, hepatitis C, or HIV. Testing for these is not mandatory unless clinically indicated-Sensory/motor neuropathy greater than or equal to G2, as defined by NCI CTCAE 4.0 -Life expectancy of less than 3 months-History of another malignancy within 5 years prior to registration. Patients with a past history of adequately treated carcinoma-in-situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or superficial transitional cell carcinoma of the bladder are eligible. Patients with a history of other malignancies are eligible if they have been continuously disease free for at least 5 years after definitive primary treatment-Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol-Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal, infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to registration. Men must have been surgically sterilised or use a (double if required) barrier method of contraception

Query!

Study design

Purpose of the study

Treatment

Query!

Allocation to intervention

Randomised controlled trial

Query!

Procedure for enrolling a subject and allocating the treatment (allocation concealment
procedures)

Query!

Methods used to generate the sequence in which subjects will be randomised (sequence
generation)

Query!

Masking / blinding

Open (masking not used)

Query!

Who is / are masked / blinded?

Query!

Query!

Query!

Query!

Intervention assignment

Parallel

Query!

Other design features

Query!

Phase

Phase 2

Query!

Type of endpoint(s)

Safety/efficacy

Query!

Statistical methods / analysis

Query!

Recruitment

Recruitment status

Recruiting

Query!

Date of first participant enrolment

Anticipated

19/08/2016

Query!

Actual

17/11/2016

Query!

Date of last participant enrolment

Anticipated

Query!

Actual

Query!

Date of last data collection

Anticipated

Query!

Actual

Query!

Sample size

Target

70

Query!

Accrual to date

19

Query!

Final

Query!

Recruitment in Australia

Recruitment state(s)

NSW,QLD,SA,TAS,WA,VIC

Query!

Recruitment outside Australia

Country [1]78670

New Zealand

Query!

State/province [1]78670

Query!

Funding & Sponsors

Funding source category [1]2935530

Government body

Query!

Name [1]2935530

National Health and Medical Research Council

Query!

Address [1]2935530

National Health and Medical Research CouncilGPO Box 1421Canberra ACT 2601

Query!

Country [1]2935530

Australia

Query!

Primary sponsor type

Other Collaborative groups

Query!

Name

Australasian Gastro-Intestinal Trials Group (AGITG)

Query!

Address

Locked Bag 77 CamperdownNSW 1450

Query!

Country

Australia

Query!

Secondary sponsor category [1]2923690

None

Query!

Name [1]2923690

Query!

Address [1]2923690

Query!

Country [1]2923690

Query!

Ethics approval

Ethics application status

Approved

Query!

Ethics committee name [1]2950220

The Northern Sydney Local Health District Human Research Ethics Committee (NSLHD HREC)

The primary purpose of this trial is to evaluate the safety and efficacy of carboplatin plus nab-paclitaxel in comparison with carboplatin plus etoposide chemotherapy for the treatment of gastrointestinal neuroendocrine carcinomas (NECs). Who is it for? You may be eligible to enrol in this trial if you are aged 18 or over, and have been diagnosed with advanced and/or metastatic, unresectable gastrointestinal neuroendocrine carcinoma (NEC). Study details All participants enrolled in this trial will be randomly allocated (by chance) to receive either carboplatin plus nab-paclitaxel or carboplatin plus etoposide. Participants receiving carboplatin plus nab-paclitaxel will be required to visit the study site once per week, for weekly administration of nab-paclitaxel plus adminstration of carboplatin once every three weeks. Participants receiving carboplatin plus etoposide will be required to visit the study site for three consecutive days every three weeks for administration of etoposide plus adminstration of carboplatin once every three weeks. Treatment will continue for all participants until disease progression or until side effects become unmanageable. All participants will be reviewed for side effects, outcomes of survival and cancer progression. Blood and tissue samples will also be taken, as well as specialised scans, to identify markers of prognosis and response. It is hoped that the findings of this trial will identify which treatment is the most promising, for further investigation to be undertaken to guide best practice.